Our ongoing research is concerned directly or indirectly with the regulation of immunity by complementary idiotypes expressed on Igs and B and T cell receptors. The concept of complementary idiotypes includes two essential ideas: 1) complementary responses may be stimulated by a single epitope since the idiotype of the response is potentially immunogenic, and 2) the product of either complementary response can potentially regulate the other response. Presumably this netwark of idiotypes evolved so that regulated responses appropriate in type, magnitude and duration were selected for which protected individuals against injurious agents. On the other hand the system may fail in some situations for reasons which are inherent in networks. Signals may be balanced or neutralized so that responses oscillate or are under or over regulated. Presumably analogous type balancing or neutralizing of inputs and outputs may account for deregulation of immunity observed in some allergies and autiommune or "immune complex" diseases. In our laboratory regulation and deregulation are studied in mice immunized with complementary antigens or idiotypes, in mice bearing plasmacytomas, and in mice bearing nonlymphoid tumors. Of course the long term challenge is to derive ways to specifically manipulate the system to induce effective autoimmunity to cancer, to prevent allograft rejection, and to turn off undesirable responses in allergies and autoimmune diseases. Recognition of the system as a complex network helps explain why these objectives are so difficult and will probably require manipulation of multiple components to achieve desired regulation. But presumably manipulation must be focused on connectivity between receptor for epitope and receptor for receptor to achieve a high degree of specific regulation.